Breathing assistance apparatus for delivery of nitric oxide to a patient by means of a nasal cannula assembly with flow control passage

ABSTRACT

The invention concerns a breathing assistance apparatus having a source of Nitric Oxide in fluid communication with a nasal cannula assembly ( 10 ) adapted to deliver gases to a patient comprising a first compartment ( 1 ) and a second compartment ( 2 ) separated by a separation wall ( 6 ); a pair of nasal prongs ( 5 ) in fluid communication with the first compartment ( 1 ); the first compartment ( 1 ) comprising a first inlet ( 11 ) for introducing a first gas into said first compartment ( 1 ); the second compartment ( 2 ) comprising a second inlet ( 2 ) for introducing a second gas into said second compartment ( 2 ); and the separation wall ( 6 ) comprising at least one flow restriction element ( 35 ) for controlling the passage of gas from the second compartment ( 2 ) to the first compartment ( 1 ).

BACKGROUND OF THE INVENTION

Field of the Invention

The invention concerns a nasal cannula assembly adapted to deliver gasesto a patient, especially for NO gas therapy, a breathing assistanceapparatus comprising such a nasal cannula assembly, and a method fortreating pulmonary vasoconstriction in a patient using such a nasalcannula assembly and/or breathing assistance apparatus.

Description of the State of the Art

NO/nitrogen gas mixtures are commonly used for treatingvasoconstrictions of the lung and pulmonary hypertension in adults andinfants.

For instance, EP-A-1516639 discloses a gaseous mixture consisting of NOand an inert gas, preferably nitrogen, used for the production of aninhalable medicament for treating persistent pulmonary hypertension ofthe newborn.

Before being inhaled by the patient, the NO/N₂ mixture is generallydiluted in an oxygen-containing gas, such as air or a O₂/N₂ mixture,comprising at least 21 vol. % of oxygen.

Typically, NO is present in the final mixture in an amount of several(1-800, most often 5-80) ppm in volume.

However, as NO is rapidly oxidized into NO₂ in the presence of oxygen,it is important to avoid long residence times in gas administrationapparatus between the point of mixing of the NO/N₂ mixture with theoxygen containing gas and inhalation by the patient, in order to keepthe concentration of NO₂ in said inhalable medicament at less than 5ppm, ideally less than 1 ppm, in the inhaled gas mixtures because NO₂ isa highly toxic gas.

NO gas mixtures are delivered by modified ventilation devices or specialmodules added to standard ventilators. Such devices are well known andtaught, for instance, by U.S. Pat. Nos. 5,558,083; 5,873,359; 5,732,693;and 6,051,241.

Current NO delivery systems are designed for use with ventilators orother breathing gas delivery devices in a hospital or transport setting.Systems to deliver NO to ambulatory patients are in development. Themajority of delivery devices are pulsed, sequential, or proportionaldelivery systems that sense the start of patient inhalation and use oneor more electronically controlled valves or switches to deliver asequenced flow of NO to the patient interface, for example anendotracheal tube, a facemask, or a nasal cannula.

For example, U.S. Pat. No. 6,089,229 discloses a device comprisingsensing means for sensing the initiation of an inhalation of a patientand a delivery means responsive to the sensing means.

Further, U.S. Pat. No. 6,142,147 teaches an apparatus with a pressuresensor and a valve controller which is responsive to the pressuresensor, and which selectively connects a first port to a second port,said second port being connected to a source of NO gas, when a negativepressure event is sensed. Here the negative pressure event would becaused by a patient's inhalation so that again a means of sensing thepatient's inhalation is used.

Furthermore, U.S. Pat. No. 6,581,599 deals with a method of deliveringNO that includes detecting the onset of inspiration.

If adapted for NO delivery to ambulatory patients, such systems sufferfrom the requirements of a source of electrical power and the need forelectromechanical parts to sense and administer sequenced pulses of NO,both of which increase the size of the system, and limit itsportability. In addition, due to inevitable lags in timing betweendetection of the start of patient inhalation and operation of dosingvalves, these systems risk delivering their pulses too late in theinhalation, such that a significant fraction of NO is exhaled.

However, there is sufficient evidence to suggest that long term NOtherapy may be beneficial for some therapeutic indications, e.g. intreating pulmonary arterial hypertension. For these long term therapies,alternative delivery systems are needed for ambulatory patients. This iscomparable to the need for devices for outpatient and in-home oxygentherapy.

For this purpose, a delivery system convenient for use by ambulatorypatients, requiring a minimum of electromechanical parts, is required sothat they can follow their NO treatment after they have left thehospital setting.

One common patient interface for home oxygen delivery is a standard formnasal cannula. Nasal cannulas are well known and widely used to deliversupplemental oxygen to patients suffering from a wide variety ofrespiratory and cardiovascular diseases. Generally, one end of an oxygensupply tubing is connected to a source of oxygen, and the other end ofthe tubing splits into two branches that meet to form a loop, where aset of two nasal prongs are positioned on that loop. The nasal prongsare inserted into a patient's nares, and a constant or time-pulsed flowof oxygen regulated by the source is sent through the tubing and the twobranches of the loop so as to exit through the nasal prongs into thepatient's nares. During inspiration, the patient inhales oxygen from theprongs together with entrained room air that is drawn through the spacebetween the nasal prongs and the walls of the patient's nares. Duringexhalation, the patient exhales through the space between the nasalprongs and the walls of the patient's nares, and in the case of aconstant oxygen supply flow, oxygen continues to exit into the patient'snares, such that much of this oxygen is carried with the expiratory flowinto the surrounding room air. Pulsed oxygen delivery devices attempt toconserve oxygen by sensing the patient's breathing cycle, and thendelivering a short-duration flow or pulse of oxygen through a nasalcannula only during inhalation, so as to avoid losing oxygen to the roomair during exhalation. As nasal cannulas are standard in the delivery ofsupplemental oxygen, many variants exist. For example, U.S. Pat. No.4,535,767 to Tiep et al. describes an oxygen delivery apparatusconsisting of a reservoir cannula, a version of which is available as acommercial product called the Oxymizer from Chad Therapeutics, asdescribed, for example by Dumont and Tiep (Using a reservoir nasalcannula in acute care; Crit Care Nurse 2002; 22:41-46). This reservoircannula includes a chamber in fluid communication with both the oxygensupply line and nasal prongs. The chamber is enclosed in part by aflexible diaphragm that collapses upon inhalation so as to empty itscontents through the nasal prongs while at the same time blocking flowfrom the oxygen supply line to the chamber. The flexible diaphragm thenexpands during exhalation to fill the chamber with exhaled gas whilere-establishing flow from the oxygen supply line into the chamber, suchthat oxygen from the supply line mixes with and displaces the exhaledgas through the nasal prongs. This type of reservoir cannula has foundutility in supplying supplemental oxygen to patients, but is ill-suitedfor supplying patients with NO/nitrogen gas mixtures in place of oxygen.First, reservoir cannulas as previously described contain means toconnect to only a single source of gas; however because commercialNO/nitrogen gas mixtures contain no oxygen, patients may require anadditional source of supplemental oxygen. Second, even if air entrainedfrom the room during inhalation provides sufficient oxygen to meet apatient's demand, it is not acceptable that oxygen-containing gasexhaled by the patient mix with NO-containing gas supplied to thechamber. It is well known that NO and oxygen react over time to produceNO₂, which is toxic even at relatively low concentrations (e.g. above 5ppm short term or even 1 ppm for long term), and as such it is wellaccepted that the residence time during which NO is brought into contactwith oxygen should be minimized when supplying these gases to a patient.Finally, the Oxymizer cannula delivers 20 mL of oxygen to the patienteach breath. For commonly supplied concentrations of medical NO/nitrogengas mixtures (e.g. containing 800 ppm NO in balance nitrogen) thisdelivered volume risks exposing the patient to too high a concentrationof NO and too low a concentration of oxygen, especially for youngerpatients with tidal volumes less than ˜200 ml, or for adult patientsexhibiting rapid, shallow breathing.

Another nasal cannula variant that exists is commonly referred to as adual-lumen nasal cannula. For example TeleFlex Hudson RCI Dual LumenCannulas are commercially available. These cannulas connect throughtubing to a source of oxygen and to a pressure sensing instrument, bothof which are in fluid communication with a pair of nasal prongs, thecross section of each prong being split into two sections (or lumen) bya wall, with one section in fluid communication with the source ofoxygen, and the other section in fluid communication with the pressuresensing instrument. While it is possible that one could conceive ofconnecting a source of NO-containing gas in place of the pressuresensing instrument in order to supply both NO and oxygen simultaneouslythrough the dual-lumen cannula, no reservoir, chamber, or othermechanism is included to control the flow of gases. To provide a pulseddelivery of NO, one would need to rely on the systems described abovethat sense the start of patient inhalation and use one or moreelectronically controlled valves or switches to deliver a sequencedpulse of NO.

BRIEF SUMMARY OF THE INVENTION

A main goal of the invention is to provide a delivery system convenientfor use by ambulatory patients, which allows nitric oxide (NO) to beefficiently administered over extended time periods, i.e. hours, days,weeks, through nasal prongs in a manner that minimizes delivery into theanatomical dead volume at the end of inhalation, and therefore alsominimizes exhalation of NO. In so doing, the system must avoid bringingNO-containing gas into contact with oxygen-containing gas until justprior to delivery to the patient, so as to avoid or minimize productionof toxic NO₂ gas through reaction of NO with oxygen.

Another goal is to provide a delivery system that, in contrast to pulseddelivery systems described in prior art, does not require a sensor todetect the onset of inspiration nor any processing unit (such as a PLCor programmable computer) or other electronics.

A solution according to the present invention concerns a nasal cannulaassembly adapted to deliver gases to a patient comprising:

-   -   a first compartment and a second compartment separated by a        separation wall,    -   a pair of nasal prongs in fluid communication with the first        compartment,    -   the first compartment comprising a first inlet for introducing a        first gas into said first compartment,    -   the second compartment comprising a second inlet for introducing        a second gas into said second compartment, and    -   the separation wall comprising at least restriction flow element        for controlling the passage of gas from the second compartment        to the first compartment.

Depending on the embodiment, the nasal cannula assembly according to thepresent invention can comprise one or several of the following features:

-   -   the separation wall comprises at least two valve elements.    -   the first compartment comprises a first inlet forming a side        gases entry in fluid communication with a gas transport conduct.    -   the nasal cannula assembly further comprises a hollow body        comprising an internal chamber comprising at least the first        compartment.    -   at least the first compartment is part of a hollow body forming        a gas conduct or a manifold.    -   said hollow body and said pair of nasal prong are integrally        molded from a soft plastics material.    -   the prongs are detachable from said hollow body to allow        different sized prongs to be placed on said hollow body to suit        different sized patients.    -   the restriction flow elements have reentrant apertures for        limiting the return flow of gas.    -   a pair of restriction flow elements is arranged in the        separation wall, directly opposite the pair nasal prongs.    -   the second compartment comprises a deformable wall.    -   the second compartment forms a deformable-wall reservoir        comprising an internal volume for the gas, when fully inflated,        of about 0.5 to 5 ml.

The present invention also concerns a breathing assistance apparatuscomprising:

-   -   a source of NO-containing gas, and    -   a nasal cannula assembly according to the present invention in        fluid communication with said source of NO-containing gas.

Depending on the embodiment, the breathing assistance apparatusaccording to the present invention can comprise one or several of thefollowing features:

-   -   breathing assistance apparatus further comprises a source of an        oxygen-containing gas in fluid communication with the nasal        cannula assembly.    -   said source of NO-containing contains NO and nitrogen.    -   said source of NO-containing contains up to 3000 ppm in volume        of NO in a balance of nitrogen.

The present invention also concerns a method for treating pulmonaryvasoconstriction in a patient, comprising:

a) providing a nasal cannula assembly according to the presentinvention, and

b) providing a therapeutically-effective amount of a NO-containing gasto said patient through said nasal cannula assembly for inhalation.

Depending on the embodiment, the nasal cannula assembly according to thepresent invention can comprise one or several of the following features:

-   -   the patient is an adult, an infant or a newborn.    -   pulmonary vasoconstriction is associated with persistent        pulmonary hypertension of the newborn.    -   pulmonary vasoconstriction is associated with pulmonary arterial        hypertension.    -   the NO-containing gas is mixed with an oxygen-containing gas        just before being inhaled by the patient.    -   the NO-containing gas is a NO/nitrogen mixture.    -   the NO-containing gas consists in a NO/nitrogen mixture        containing up to 3000 ppm by volume of NO.    -   the O₂-containing gas is air or an O₂/N₂ mixture containing at        least 21 vol. % of O₂.

The invention may be further defined in some embodiments by one or moreof the following numbered sentences:

1. A nasal cannula assembly (10) adapted to deliver gases to a patient,the nasal cannula assembly (10) comprising:

a) a hollow body (4) configured to be capable of acting as a gas conductor a gas manifold and comprising an internal chamber (7) defining afirst compartment (1),

b) the first compartment (1) and a second compartment (2) separated by aseparation wall (6),

c) a pair of nasal prongs (5) in fluid communication with the firstcompartment (1),

d) the first compartment (1) comprising a first inlet (11) forming aside gases entry in fluid communication with a gas transport conduct andconfigured to conduct a first gas into said first compartment (1),

e) the second compartment (2) having a fully inflated internal volumefor a gas of about 0.5 to 5 ml, the second compartment (2) comprising,

-   -   a second inlet (12) configured to conduct a second gas into said        second compartment (2), and    -   a deformable wall (14) forming a part of the boundary between        the second compartment (2) and the room atmosphere such that the        Compliance of the second compartment (2) is not less than 5        ml/cm H₂O while filling but is less than 0.1 ml/cm H₂O once the        second compartment (2) is full,

f) the separation wall (6) comprising at least two flow restrictionchannels (35)

-   -   A) having a rounded edge at the entrance from second compartment        (2) and    -   B) having a reentrant aperture at the exit into first        compartment (1) and    -   C) which are oriented and arranged in the separation wall (6)        directly opposite the pair nasal prongs (5) to thereby be        capable of        -   permitting a passage of gas from the second compartment (2)            to the first compartment (1) in a reduced pressure state            during an inhalation phase and        -   preventing a majority of flow of the second gas from the            second compartment (2) to first compartment (1) in a higher            pressure state, during an exhalation phase, relative to the            passage of gas during a reduced pressure state, during an            inhalation phase, such that during a higher pressure state            exhalation phase the majority of flow of the second gas            entering the second compartment (2) from the second inlet            (12) is retained in the second compartment (2) causing the            deformable wall (14) to deform and increase the volume of            the second compartment (2) by at least one cubic centimeter            in volume or by at least 50% volume, or both, as compared to            the second compartment (2) volume at the end of the previous            reduced pressure state inhalation phase.            2. A nasal cannula assembly (10) adapted to deliver gases to            a patient, the nasal cannula assembly (10) comprising:

a) a first compartment (1) and a second compartment (2) separated by aseparation wall (6),

b) a pair of nasal prongs (5) in fluid communication with the firstcompartment (1),

c) the first compartment (1) comprising a first inlet (11) configured toconduct a first gas into said first compartment (1),

d) the second compartment (2) comprising a second inlet (12) configuredto conduct a second gas into said second compartment (2), and

e) the separation wall (6) comprising at least one flow restrictionchannel (35) configured to

-   -   permit a passage of gas from the second compartment (2) to the        first compartment (1) a reduced pressure state during an        inhalation phase and    -   prevent a majority of flow of the second gas from the second        compartment (2) to first compartment (1) in a higher pressure        state, during an exhalation phase, relative to the passage of        gas during a reduced pressure state, during an inhalation phase.        3. The nasal cannula assembly according to Sentence 2, wherein        the separation wall (6) comprises at least two flow restriction        channels (35).        4. The nasal cannula assembly according to Sentence 2 or 3,        wherein the first compartment (1) comprises a first inlet (11)        forming a side gases entry in fluid communication with a gas        transport conduct.        5. The nasal cannula assembly according to Sentence 2, 3 or 4,        wherein the nasal cannula assembly further comprises a hollow        body (4) comprising an internal chamber (7) comprising at least        the first compartment (1).        6. The nasal cannula assembly according to Sentence 2, 3, 4 or        5, wherein at least the first compartment (1) is part of a        hollow body (4) configured to be capable of acting as a gas        conduct or a gas manifold.        7. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        or 6, wherein said hollow body (4) and said pair of nasal prong        (5) are integrally molded from a soft plastics material.        8. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6 or 7, wherein the prongs (5) are detachable from said hollow        body (4) and selected from different sized prongs suitable for        different sized patient nares.        9. The nasal cannula assembly according to Sentence 3, 4, 5, 6,        7 or 8, wherein the two flow restriction channels (35) connect        the first compartment (1) and second compartment (2) and are        rounded edged at the entrance from second compartment (2) and        have a reentrant aperture at the entrance from the first        compartment (1).        10. The nasal cannula assembly according to Sentence 3, 4, 5, 6,        7, 8 or 9, wherein the two flow restriction channels (35) are        arranged in the separation wall (6), directly opposite the pair        nasal prongs (5).        11. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9 or 10, wherein the second compartment (2) comprises a        deformable wall (14).        12. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10 or 11, wherein the second compartment (2) forms a        deformable-wall reservoir comprising a fully inflated internal        volume for the gas of about 0.5 to 5 ml.        13. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10, 11 or 12, wherein nasal cannula assembly does        not comprise a sensor configured to detect an onset of patient        inspiration.        14. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10, 11, 12 or 13, wherein the two flow restriction        channels (35) prevent a majority of flow of the second gas from        the second compartment (2) to first compartment (1) in a higher        pressure state, during an exhalation phase, relative to the        passage of gas during a reduced pressure state, during an        inhalation phase, optionally further causing the deformable wall        (14) to deform and increase the volume of the second compartment        (2) by at least one cubic centimeter in volume or by at least        50% volume, or both, as compared to the second compartment (2)        volume at the end of the previous reduced pressure state        inhalation phase.        15. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10, 11, 12, 13 or 14, wherein the two flow        restriction channels (35) prevent >70% of flow of the second gas        from the second compartment (2) to first compartment (1) in a        higher pressure state, during an exhalation phase, relative to        the passage of gas during a reduced pressure state, during an        inhalation phase.        16. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, wherein the two flow        restriction channels (35) prevent >90% of flow of the second gas        from the second compartment (2) to first compartment (1) in a        higher pressure state, during an exhalation phase, relative to        the passage of gas during a reduced pressure state, during an        inhalation phase.        17. The nasal cannula assembly according to Sentence 11, 12, 13,        14, 15 or 16, wherein the deformable wall (14) of the second        compartment (2) has a greater Compliance while filling than when        the second compartment (2) is full.        18. The nasal cannula assembly according to Sentence 2, 3, 4, 5,        6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17, wherein the nasal        prongs (5) includes an external pillow element (8) at an end.        19. The nasal cannula assembly according to Sentence 18, wherein        said pillow elements (8) is made of silicone.        20. The nasal cannula assembly according to claim 1, further        comprising one or more orifices (13) between the first        compartment (1) defining an internal chamber (7) and an external        atmosphere.        21. The nasal cannula assembly according to claim 9, wherein a        diameter of the two flow restriction channels (35) is between        0.1 mm and 5 mm, and he two flow restriction channels (35)        comprise rounded edges at an entrance to the two flow        restriction channels (35) designed such that the ratio between a        radius of curvature of the rounded edges and the diameters of        the two flow restriction channels (35) is greater than 0.02.        22. A breathing assistance apparatus comprising:

a) a source of NO-containing gas, and

b) a nasal cannula assembly according to one or more of NumberedSentence 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, or 21, in fluid communication with said source of NO-containinggas.

23. A breathing assistance apparatus according to Numbered Sentence 22,wherein the breathing apparatus further comprises a source of anoxygen-containing gas in fluid communication with the nasal cannulaassembly.

24. A breathing assistance apparatus according to Numbered Sentence 22,wherein said source of NO-containing contains NO and nitrogen.

25. A breathing assistance apparatus according to Numbered Sentence 22,wherein said source of NO-containing contains from 1 ppm to 5000 ppm involume of NO in a balance of nitrogen.

26. A method for treating pulmonary vasoconstriction in a patient,comprising:

a) providing a nasal cannula assembly according to one or more ofNumbered Sentence 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, or 21, and

b) providing a therapeutically-effective amount of a NO-containing gasto said patient through said nasal cannula assembly for inhalation tothereby reduce the pulmonary vasoconstriction in the patient.

27. The method according to Numbered Sentence 26, wherein the patient isan adult, an infant or a newborn.

28. The method according to Numbered Sentence 26, wherein pulmonaryvasoconstriction is associated with persistent pulmonary hypertension ofthe newborn.

29. The method according to Numbered Sentence 26, wherein pulmonaryvasoconstriction is associated with pulmonary arterial hypertension.

30. The method according to Numbered Sentence 26, wherein theNO-containing gas is mixed with an oxygen-containing gas just beforebeing inhaled by the patient.

31. The method according to Numbered Sentence 26, wherein theNO-containing gas is a NO/nitrogen mixture.

32. The method according to Numbered Sentence 26, wherein theNO-containing gas consists in a NO/nitrogen mixture containing from 1ppm to 5000 ppmv of NO.

33. The method according to Numbered Sentence 26, wherein theO₂-containing gas is air or an O₂/N₂ mixture containing at least 21% (byvolume) of O₂.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The present invention will be better understood thanks to the followingdescription and explanation made in reference to the Figures, wherein:

FIG. 1 is a schematic of a first embodiment of a nasal cannula assemblyaccording to the present invention,

FIG. 2 is a schematic of a second embodiment of a nasal cannula assemblyaccording to the present invention having nasal nare pillows (8) forsecuring the cannula to the nares,

FIGS. 3A-D show a schematic of a second embodiment of a nasal cannulaassembly according to the present invention with gas flow illustrated inthe inhalation and exhalation phases with supplemental Oxygen (3A-B) andwithout supplemental Oxygen (3C-D), and

FIG. 4 displays an estimated pattern of inhaled NO concentration thatcould be achieved using a nasal cannula assembly according to thepresent invention,

FIG. 5 shows a schematic of a working model for validating restrictionflow channel (35) performance under simulated breathing conditions, withelements labeled as follows:

-   -   [40]—Lung Simulator (ASL 5000; Ingmar Medical)    -   [22]—22 mm straight connector with sampling port    -   [30]—Gas sampling line to NO analyzer (Siemens NOA 280i; GE)    -   [21]—22 mm T piece connector    -   [23]—22 mm straight connector    -   [24]—Step-down connector, 22 mm to 4 mm    -   [35 a]—4 mm flow restriction channel; internal to connector [23]    -   [25]—22 mm straight connector with injection port    -   [90]—NO injection line    -   [26]—Breathing filter (ClearGuard II; Intersurgical),

FIG. 6 shows results of an exemplary experiment using the testingapparatus of FIG. 5: Flow (top) and pressure (bottom) versus timewaveforms obtained from the lung simulator with no filter. The X-axisunits are seconds, while the Y-axis units are L/min and cm H2O,respectively,

FIG. 7 shows results of an exemplary experiment using the testingapparatus of FIG. 5: Flow (top) and pressure (bottom) versus timewaveforms obtained from the lung simulator with the filter in place. TheX-axis units are seconds, while the Y-axis units are L/min and cm H₂O,respectively, and

FIG. 8 shows results of an exemplary experiment using the testingapparatus of FIG. 5: Top row: flow versus time waveforms from the lungsimulator obtained with no filter (left) and with the filter in place(right). Bottom row: NO concentration versus time waveform as sampledfrom the first compartment [1] with no filter (left) and with the filterin place (right).

DETAILED DESCRIPTION OF THE INVENTION

A schematic of a first embodiment of the nasal cannula assembly of thepresent invention is shown in FIG. 1 (in cross section).

The nasal cannula assembly of the present invention is a patientinterface generally comprising a pair of nasal prongs 5 coupledindirectly to a deformable-wall 14 having a reservoir 2 supplied with NOcontained in nitrogen (12), e.g. at 225, 450, 800 or 1000 ppm in volume.

The pair of nasal prongs 5 is positioned on a hollow body 4, for examplean air or oxygen conduit or manifold, comprising an internal hollowvolume or chamber 7 thereby forming a first compartment 1 that receivesthe gases.

The nasal prongs 5 are small conduits or tubes adapted for insertioninto the nares of a patient and through which passes the gas mixturethat is subsequently inhaled by the patient. Each prong 5 comprises anoutlet orifice 15 at its end.

The hollow body 4 can be made of a rigid light material, such as polymeror similar. Preferably, the hollow body 4 and the pair of nasal prong 5are integrally molded from a soft plastics material. However, the prongs5 can also be detachable from said hollow body 4 to allow differentsized prongs to be placed on said hollow body 4 to suit different sizedpatients, such as adults and infants. The hollow body 4 is in turn influid communication via fluid transfer elements 30, such as flowrestriction channel(s), with reservoir 2 formed by the deformable-wall14 and separation wall 6. In other words, the nasal cannula assembly ofthe present invention is split into two main inhaled gas compartments 1and 2 that are separated each from the other by a separation wall 6.

The second compartment 2 forms a deformable reservoir receiving the NOgas through an inlet 12. The deformable wall 14 of the reservoir orsecond compartment 2 should be made from a thin, flexible sheet ofpolymer material so that the reservoir readily inflates duringexhalation, but collapses, at the start of inhalation. In this manner,NO-containing gas is allowed to accumulate in the reservoir while thepatient exhales, and then is released as a bolus at the start ofinhalation as the reservoir collapses and its contents empty through thefluid transfer elements 30, such as flow restriction channel(s), intothe first compartment 1. Throughout this cycle a constant flow ofNO-containing gas may be maintained through the inlet 12.

The second compartment 2 fluidly communicates with the first compartment1 through one or more fluid transfer elements 30 as shown in FIG. 1.These fluid transfer elements are arranged in the separation wall 6.Preferably, as shown in FIG. 1, two fluid transfer elements 30 arepositioned along the conduit 7 forming the hollow main body 4, directlyopposite the nasal prongs 5, i.e. each fluid transfer elements 30 isfacing one nasal prong 5, so as to facilitate the gas circulation fromthe second compartment 2 to the first compartment 1 and subsequently tothe nasal prongs 5.

The fluid transfer elements 30 are generally one or more flowrestriction channel(s) 35 connecting first compartment 1 to secondcompartment 2 (FIG. 1). The flow restriction channel 35 should beadapted by dimension to limit the majority of flow of NO from secondcompartment 2 to first compartment 1 (i.e. >50% such as 60, 70 80 or90%) in the higher pressure state during an exhalation phase relative tothe reduced pressure state during an inhalation phase. The flow ratedifferential between the two pressure conditions may be adjusted byselecting the appropriate flow restriction 35 dimensions (e.g. tubularsize), a degree of baffling in the flow restriction channel 35, and/orany other suitable flow restriction elements (e.g. membranes, particlepacking, constrictions, etc.). Independent of the specific geometricadaptation, the flow restriction element may be characterized by theequation:

${{\Delta\; P} = {\frac{1}{2}\rho\;{KV}^{2}}},$where ΔP indicates the pressure drop associated with flow of a fluidwith density ρ through the flow restriction element at a velocity Vrepresenting the mean fluid velocity through the flow restrictionelement, as averaged, e.g., over the cross-section of the entrance tothe element. The coefficient K depends on the geometry and configurationof the flow restriction element, and may thus be used to characterizethe flow restriction element, where a larger value of the coefficient Kis associated with a larger pressure drop through the flow restrictionelement for a given fluid density ρ of a fluid traveling at a given meanvelocity V. In other words, a larger value of the coefficient K isassociated with a lower mean flow velocity V when a given pressure dropΔP is imposed across the flow restriction element. Therefore a flowrestriction element with larger coefficient K will in general representa larger barrier to flow through that element.

In light of this understanding, one adaptation of the flow restrictionchannel 35 connecting first compartment 1 to second compartment 2 is anorifice with dimension selected to produce a coefficient K sufficientlylarge in value to limit flow from compartment 2 to compartment 1 throughthe flow restriction channel during the higher pressure state, where thehigher pressure in compartment 1 is associated with a small pressuredrop ΔP imposed across the orifice, but at the same time sufficientlysmall in value to permit flow from compartment 2 to compartment 1through the flow restriction channel during the reduced pressure state,where the reduced pressure in compartment 1 is associated with a largerpressure drop ΔP imposed across the orifice. A circular orifice withdiameter between around 0.1 mm and around 5 mm, and specifically between0.5 mm and 2 mm serves as a reasonable solution for many patientbreathing patterns. Orifices of different geometry (e.g. an oval, asquare, or a slot) but of similar dimension are also reasonablesolutions.

A second adaptation of the flow restriction channel 35 connecting firstcompartment 1 to second compartment 2 is a constriction channel (FIGS.3A & 3B) designed such that the constriction channel has a rounded edgeat the entrance from compartment 2 for flow in the direction fromcompartment 2 into compartment 1. Further, the constriction channelprotrudes into compartment 1 so as to create a reentrant type entrancefor flow in the reverse direction from compartment 1 into compartment 2.It is known that the coefficient K defined above is considerably largerfor a reentrant-type entrance than for a rounded-edged entrance, thus inthe context of the flow restriction channel discussed here, use of aconstriction channel as described above will provide little resistanceto flow in the direction from compartment 2 into compartment 1 but willresist flow in the direction from compartment 1 to compartment 2.Accordingly, the constriction channel provides a further advantage forcontrolling the direction of flow between compartment 1 and compartment2 in addition to performing the function of modulating flow fromcompartment 2 to compartment 1 between higher and reduced pressurestates as described above for the flow restriction channel in general.The diameter of the constriction channel should generally be betweenaround 0.1 mm and around 5 mm, and specifically between 0.5 mm and 2 mm.The rounded edges at the entrance to the constriction channel should bedesigned such that the ratio between the radius of curvature of the edgeand the diameter of the constriction is greater than 0.02, preferablygreater than 0.1; however, increasing this ratio beyond a value of about0.15 provides little further benefit. For general guidance onrestriction flow channel design, see Fox and McDonald, Introduction toFluid Mechanics, Fifth edition, John Wiley & Sons, NY, 1998, Chapter 8,or Shaughnessy, Katz, and Schaffer, Introduction to Fluid Mechanics,Oxford University Press, NY, 2005, Chapter 13.

In any case, the combination of flow restriction channel(s) 35 anddeformable wall 14 of the embodiment depicted in FIG. 1 should beresponsive to increases and decreases in pressure that develop duringexhalation and inhalation, respectively, so as to allow the deformablereservoir 2 to inflate with NO-containing gas during exhalation, andthen empty to release this gas through the flow restriction channel(s)35 into the first compartment 1 during inhalation.

Generally the deformable wall 14 needs to be of a thin, flexiblematerial such that zero or near zero positive pressure above atmosphericdevelops in compartment 2 as it fills from the Nitric Oxide flow 12during exhalation (so that flow of gas through the restrictionchannel(s) 35 remains minimal during exhalation while the bag fills).Reservoir 2 thus should be designed preferably to have infinite or nearinfinite Compliance (where Compliance=deltaVolume/deltaPressure), whilefilling—and then drop to zero or near zero Compliance once full.

The first compartment 1 is supplied with an oxygen-containing gasthrough a first inlet port 11, whereas the second compartment 2 forminga NO-reservoir is supplied with a constant flow of NO-containing gasthrough a second inlet port 12.

During patient exhalation, the second compartment or reservoir 2 fillswith NO containing gas, whereas, during patient inhalation,NO-containing gas mixes with air and/or oxygen in the first compartment1 as it is inhaled by the patient through the prongs 5.

The volume of the second compartment 2 is configured and sized so as tobe small compared to the patient's inhaled tidal volume, so that thesecond compartment 2 quickly empties during the initial period of theinhalation phase to create a bolus of elevated NO concentration at thestart of the inhalation.

Normally high concentrations of NO, e.g. 800 vol. ppm of NO in nitrogen,are delivered to the second compartment 2 from a source of NO/N₂, suchas a gas cylinder with integrated pressure regulator and flow meteringapparatus.

Patient safety is ensured by supplying only low flows of NO-containinggas. For example, to deliver to the patient an amount of NO equivalentto that delivered during continuous supply of gas containing 5 ppmv NOthroughout the duration of a 500 ml tidal breath, about 3 ml of gascontaining 800 ppmv NO should be supplied each breath.

During tidal breathing, the expiratory time of a typical adult willrange from approximately 2 to 5 seconds. Therefore, supply flows on theorder of 1 ml/s of NO containing gas are required. In operation, the NOflow rate may be adjusted based on visual inspection of theinflation/deflation of deformable wall 14 to ensure the appropriate flowrate for a specific patient's inhalation pattern. Visual inspection ofthe inflation/deflation of the deformable wall 14 also provides feedbackto the user to ensure proper function of the device, and may be used bya healthcare practitioner in fitting a patient with appropriately sizednasal prongs.

FIG. 4 displays an estimated pattern of inhaled NO concentration thatwould be achieved using the present invention based on the numbersmentioned above.

More precisely, one can see on FIG. 4 the estimated tidal flow, firstcompartment 1 pressure, and inhaled NO concentration curves during atypical adult tidal breathing pattern using a nasal cannula assembly 10according to the present invention supplied with 1 ml/sec flow of gascontaining 800 ppmv of NO in N₂.

The breathing pattern is shown in the upper curve, with positive flowrepresenting inhalation, and negative flow representing exhalation. Thevariation of pressure within the first compartment 1 over the breathingcycle is shown in the middle curve. The estimated NO concentrationcontained in the gas mixture delivered to the patient through the nasalprongs 5 during the inhalation phase of the breathing cycle is shown inthe bottom curve.

The NO concentration spikes at the start of inhalation as NO-containinggas is released from the second compartment 2 before rapidly decreasingonce the second compartment empties.

Through the later stages of inhalation a low NO concentration isdelivered as fresh NO-containing gas supplied through inlet 12 passesinto the first chamber 1 and the nasal prongs 5.

In contrast, throughout exhalation, flow of NO-containing gas from thesecond chamber to the first chamber is prevented or at least reduced bythe flow restriction channel(s) 35.

For some patients, it may be desirable to minimize gas leaks between thenasal prongs 5 and the patient's nares, e.g. to provide continuouspositive airway pressure CPAP, Bi-level positive airway pressure(Bi-PAP), or other positive pressure support in combination with NOtherapy, or to provide additional control over the higher and reducedpressure states achieved during the breathing cycle. In suchcircumstances, the nasal cannula assembly 10 may comprise additionalelements as shown in FIG. 2.

First, each of the nasal prongs 5 includes an external pillow element 8at its ends, which is intended to more tightly secure the prongs 5inside the patient's nares or nostrils. Said pillow elements 8 can bemade of soft resilient material, such as silicone or similar.

Second, additional orifices or slots 13 are included between the firstcompartment 1 defining the internal chamber 7 and the room atmosphere,to allow entrainment of room air, e.g. during inhalation, and exhaust ofgases to the room atmosphere, e.g. during exhalation. The number anddimensions of these orifices or slots 13 may be selected so as toachieve a desired range of higher and reduced pressure states during thebreathing cycle.

WORKING EXAMPLE

To demonstrate an embodiment of the restriction flow channel of theinvention, a mechanical lung simulation device was used to produce abreathing pattern. The breathing pattern was set to that of an averageadult human. Breathing patterns representing any patient could be usedas the basis for validating a restriction flow channel design for aspecific class of patients (e.g. pediatric breathing patterns). Theexemplary experiment was performed using a single flow restrictionchannel [35 a] positioned between a first compartment [1] and a secondcompartment [2]. A 22 mm diameter straight connector [22] including aport for gas sampling via the gas sampling line [30] was positionedbetween a lung simulator (ASL 5000; Ingmar Medical) [40] and T piece[21]. A second arm of the T piece [21] was connected to a 22 mm straightconnector [23], which contained internally a 4 mm flow restrictionchannel [35 a]. The third arm of the T piece [21] was either left opento the room atmosphere, or connected to a breathing filter (ClearGuardII; Intersurgical) [26], which in turn was open to the room atmosphere.The internal conduits of the straight connector with sampling port [22],the T piece [21], and the straight connector [23] formed the firstcompartment [1]. The flow restriction channel [35 a] was connectedthrough a step-down connector [24] to a 22 mm diameter straightconnector [25] which included a port for NO gas injection from the NOgas injection line [90]. The opposite end of the straight connector [25]was open to the room atmosphere. The internal conduits of the straightconnector with injection port [25] and the step-down connector [24]formed a second compartment [2].

Flow into and out of the lung simulator and the pressure at the entranceto the lung simulator, representing the pressure throughout the firstcompartment [1], were recorded over time by the lung simulator. Theconcentration of NO in gas sampled via the gas sampling line [30] wasmonitored using a chemiluminescence NO analyzer (Siemens NOA 280i; GE).The lung simulator was programmed so as to deliver a 600 mL tidal volumebreath at a frequency of 15 breaths/minute, with a sinusoidalinspiratory waveform and a passive, mono-exponential expiratory flowpattern, and an inspiratory time to expiratory time ratio of 2 to 3. Aconstant flow of 250 mL/min of 800 ppm NO in balance nitrogen gas wasdelivered through the NO injection line [90]. FIGS. 2 and 3 display flowand pressure versus time waveforms over several breathing cycles forexperiments performed without and with the filter [27] in place,respectively. The flow waveform is not appreciably changed between thetwo experiments, while the pressure waveforms differ. With no filter inplace, FIG. 2, the pressure in the first compartment [1] oscillatesbetween a minimum of ˜−0.2 cm H₂O during inhalation and a maximum of˜0.1 cm H₂O during exhalation. With the filter [27] in place, FIG. 3,the small added resistance to air flow through the filter results in areduced pressure state reaching −1.0 cm H₂O during inhalation, and ahigher pressure state reaching 1.0 cm H₂O during exhalation.

FIG. 4 again displays flow versus time waveforms (top row) over severalbreathing cycles for experiments performed without (top left) and with(top right) the filter [27] in place. The bottom row of FIG. 4 displaysNO concentrations versus time in gas sampled from the first compartment[1] for experiments performed without (bottom left) and with (bottomright) the filter [27] in place. With no filter in place, that is withpressure states in the first compartment [1] varying between −0.2 cm H₂Oduring inhalation and 0.1 cm H₂O during exhalation, the NO concentrationin gas sampled from the first compartment [1] reached just over 10 ppmduring periods of low flow (e.g. at end-expiration), where pressure inthe first compartment [1] was near zero, and during inhalation, wherepressure in the first compartment [1] was negative, but fell to nearzero when expiratory flow rates were appreciable and the pressure in thefirst compartment [1] rose. With the filter [27] in place, such that thepressure in compartment [1] varied between a reduced pressure statereaching −1.0 cm H₂O during inhalation, and a higher pressure statereaching 1.0 cm H₂O during exhalation, the variation in delivered NOconcentration was magnified: a bolus of gas containing NO concentrationas high as 20 ppm passed through the first compartment [1] duringinhalation, and the NO concentration fell to approximately 5 ppm duringperiods where expiratory flow was appreciable, such that the higherpressure state was achieved in the first compartment [1], before risingto 10 ppm through the remainder of the breathing cycle.

While the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives,modifications, and variations will be apparent to those skilled in theart in light of the foregoing description. Accordingly, it is intendedto embrace all such alternatives, modifications, and variations as fallwithin the spirit and broad scope of the appended claims. The presentinvention may suitably comprise, consist or consist essentially of theelements disclosed and may be practiced in the absence of an element notdisclosed. Furthermore, if there is language referring to order, such asfirst and second, it should be understood in an exemplary sense and notin a limiting sense. For example, it can be recognized by those skilledin the art that certain steps can be combined into a single step.

The singular forms “a”, “an” and “the” include plural referents, unlessthe context clearly dictates otherwise.

“Comprising” in a claim is an open transitional term which means thesubsequently identified claim elements are a nonexclusive listing (i.e.,anything else may be additionally included and remain within the scopeof “comprising”). “Comprising” as used herein may be replaced by themore limited transitional terms “consisting essentially of” and“consisting of” unless otherwise indicated herein.

“Providing” in a claim is defined to mean furnishing, supplying, makingavailable, or preparing something. The step may be performed by anyactor in the absence of express language in the claim to the contrary.

Optional or optionally means that the subsequently described event orcircumstances may or may not occur. The description includes instanceswhere the event or circumstance occurs and instances where it does notoccur.

Ranges may be expressed herein as from about one particular value,and/or to about another particular value. When such a range isexpressed, it is to be understood that another embodiment is from theone particular value and/or to the other particular value, along withall combinations within said range.

All references identified herein are each hereby incorporated byreference into this application in their entireties, as well as for thespecific information for which each is cited.

The invention claimed is:
 1. A breathing assistance apparatuscomprising: a) a source of NO-containing gas, and b) a nasal cannulaassembly (10) in fluid communication with said source of NO-containinggas, the nasal cannula assembly (10) adapted to deliver gases to apatient, the nasal cannula assembly (10) comprising: A) a hollow body(4) configured to be capable of acting as a gas conduct or a gasmanifold and comprising an internal chamber (7) defining a firstcompartment (1), B) the first compartment (1) and a second compartment(2) separated by a separation wall (6), C) a pair of nasal prongs (5) influid communication with the first compartment (1), D) the firstcompartment (1) comprising a first inlet (11) forming a side gases entryin fluid communication with a gas transport conduct and configured toconduct a first gas into said first compartment (1), E) the secondcompartment (2) having a fully inflated internal volume for a gas ofabout 0.5 to 5 ml, the second compartment (2) comprising, a second inlet(12) configured to conduct a second gas into said second compartment(2), and a deformable wall (14) forming a part of a boundary between thesecond compartment (2) and a room atmosphere such that the compliance ofthe second compartment (2) is not less than 5 ml/cm H₂O while fillingbut is less than 0.1 ml/cm H₂O once the second compartment (2) is full,F) the separation wall (6) comprising two flow restriction channels (35)having a rounded edge at an entrance from the second compartment (2) andhaving a reentrant aperture at an exit into the first compartment (1)and which are oriented and arranged in the separation wall (6) directlyopposite the pair of nasal prongs (5) to thereby be capable ofpermitting a passage of gas from the second compartment (2) to the firstcompartment (1) in a reduced pressure state during an inhalation phaseand preventing a majority of flow of the second gas from the secondcompartment (2) to the first compartment (1) in a higher pressure state,during an exhalation phase, relative to the passage of gas during thereduced pressure state, during an inhalation phase, such that during thehigher pressure state exhalation phase the majority of flow of thesecond gas entering the second compartment (2) from the second inlet(12) is retained in the second compartment (2) causing the deformablewall (14) to deform and increase the internal volume of the secondcompartment (2) by at least 50% volume, as compared to the secondcompartment (2) volume at the end of the previous reduced pressure stateinhalation phase.
 2. The breathing assistance apparatus according toclaim 1, further comprising one or more orifices (13) in the firstcompartment (1) defining a fluid communication from an internal chamber(7) to an external atmosphere.